Endometrial cancer is the most commonly diagnosed malignancy of the female reproductive tract in the United States. It was estimated that 39,080 new cases of cancer of the uterine corpus would be diagnosed and 7,400 women would die of this disease in the United States in 2007 (Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun M J. CA Cancer J Clin 2007 January-February; 57(1):43-66). The majority of women presenting with endometrial cancer are surgically cured with a hysterectomy; however, about 15% of women demonstrate persistent or recurrent tumors that are refractory to current chemotherapies. For those women with advanced stage, progressive, or recurrent disease, survival is poor as there are no adjuvant therapies proven to be effective. The median survival after recurrence is ten months (Jereczek-Fossa B, Badzio A, Jassem J., Int J Gynecol Cancer 1999 July; 9(4):285-94) and the five-year survival for patients who have recurred is only 13% (Creutzberg C L, van Putten W L, Koper P C, et al., Lancet 2000 Apr. 22; 355(9213):1404-11).
Malignant carcinomas often display mutations in multiple oncogenes and tumor suppressor genes, exhibit alterations in the expression of hundreds of genes, and contain various chromosomal abnormalities. Despite this genomic complexity, targeting specific molecular abnormalities has been shown to produce rapid regression of human tumors, such as is seen with the selective tyrosine kinase inhibitors Imatinib (Gleevec) and Gefitinib (Iressa). To explain this phenomenon, Bernard Weinstein introduced the term “oncogene addiction”. He proposed that the signaling circuitry of a tumor cell is reprogrammed in the presence of an oncogenic activity such that the tumor cell is dependent on that oncogenic activity for cell survival and growth (Weinstein I B. Science 2002 Jul. 5; 297(5578):63-4). Indeed, experimental and clinical data support this concept of oncogene addiction and, furthermore, suggest that multiple mechanisms of oncogene activation, including mutation, rearrangement, and overexpression, can be involved in oncogene addiction (Weinstein I B, Joe A K., Nat Clin Pract Oncol 2006 August; 3(8):448-57).
A variety of somatic gene defects have been reported in endometrial carcinoma. Well or moderately differentiated endometrioid endometrial carcinomas account for approximately 80% of uterine cancers. They are characterized by a high frequency of inactivating mutations in PTEN (26-80%), activating KRAS2 mutations (13-26%), and gain-of-function β-catenin mutations (25-38%) (Hecht J L, Mutter G L., J Clin Oncol 2006 Oct. 10; 24(29):4783-91, Shiozawa T, Konishi I., Int J Clin Oncol 2006 February; 11(1):13-21). Germline gain-of-function mutations in FGFR1, 2, and 3 have been reported in a variety of craniosynostosis syndromes and chondrodysplasia syndromes. The genotype/phenotype correlations in these disorders are complex, with over 14 distinct clinical syndromes associated with mutations in one of the three receptors and several clinical syndromes e.g., Pfeiffer and Crouzon Syndrome associated with mutations in different receptors (Passos-Bueno M R, Wilcox W R, Jabs E W, Sertie A L, Alonso L G and Kitoh H. (1999), Hum Mutat 14: 115-125, Wilkie A O, Patey S J, Kan S H, van den Ouweland A M and Hamel B C. (2002), Am J Med Genet 112: 266-278).
Although much progress has been made toward understanding the biological basis of cancer and in its diagnosis and treatment, it is still one of the leading causes of death in the United States. Inherent difficulties in the diagnosis and treatment of cancer include among other things, the existence of many different subgroups of cancer and the concomitant variation in appropriate treatment strategies to maximize the likelihood of positive patient outcome. Furthermore, there are a wide range of endometrial cancer subgroups and variations in the disease's progression. To properly treat the endometrial cancer and to maximize the chances of a successful treatment it is important that the type or subtype of endometrial cancer be identified as early as possible.
Thus, there presently is a need for a method of detecting and classifying endometrial cancer in order to select the appropriate and optimal treatment regimen. Once detected and classified, there is a further need for improved methods of treating endometrial cancer based on the type of endometrial cancer to maximize the chances of successfully treating or inhibiting reoccurrence of the disease in the subject.